INSIDE FRONT RCOEV ES2 This page intentionally left blank THIRD EDITION Carl P. Weiner, MD, MBA, FACOG K. E. Krantz Professor and Chair Department of Obstetrics and Gynecology Division Head, Maternal Fetal Medicine Professor, Molecular and Integrative Physiology Director, Center for the Developmental Origins of Adult Health and Disease University of Kansas School of Medicine Kansas City, Kansas Professor Department of Pharmaceutical Chemistry University of Kansas School of Pharmacy Lawrence, Kansas Clifford Mason, PhD Assistant Professor Department of Obstetrics and Gynecology Assistant Professor Department of Pharmacology, Toxicology, and Therapeutics University of Kansas School of Medicine Kansas City, Kansas 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 DRUGS FOR PREGNANT AND LACTATING WOMEN, THIRD EDITION ISBN: 978-0-323-42874-3 Copyright © 2019 by Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the Publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted in 2009, 2004. Library of Congress Cataloging-in-Publication Data Names: Weiner, Carl P., author. | Mason, Clifford, 1981- author. Title: Drugs for pregnant and lactating women / Carl P. Weiner, Clifford Mason. Description: Third edition. | Philadelphia, PA : Elsevier, Inc., [2020] | Includes bibliographical references and index. Identifiers: LCCN 2018010207 | ISBN 9780323428743 (hardcover : alk. paper) Subjects: | MESH: Pregnancy–drug effects | Breast Feeding–adverse effects | Contraindications | Drug-Related Side Effects and Adverse Reactions | Fetus–drug effects | Infant | Pharmaceutical Preparations | Pregnancy Complications–chemically induced | Handbooks Classification: LCC RG627.6.D79 | NLM WQ 39 | DDC 618.3/2–dc23 LC record available at https://lccn.loc.gov/2018010207 Senior Content Strategist: Sarah Barth Senior Content Development Specialist: Anne Snyder Publishing Services Manager: Catherine Jackson Senior Project Manager: Sharon Corell Book Designer: Patrick Ferguson Printed in China. Last digit is the print number: 9 8 7 6 5 4 3 2 1 Foreword to the Second Edition This is a dream come true for all of those who care for pregnant and nonpregnant women. There is nothing like this in medical literature. In the past, I have been involved in the publications of several texts on drugs and pregnancy. This new text is on the leading edge of science and knowledge for women and drugs, with more than 720 generic drugs with their 1500 trade names listed in alphabetical order to make identification easy for each drug. Over-the-counter drugs are also included. The information provided in both hard text and electronic versions is very extensive, concise, and user friendly. Its availability as an electronic version for hand-held computer devices, that will be updated for the life of the edition, is particularly exciting. This will not only benefit all health care workers in the field of obstetrics and gynecology, but will also allow instantaneous access to drug related questions. Included in text and electronic versions are the following headings: Name Class Indications Dosage with qualifiers Maternal Considerations Fetal Considerations Breastfeeding Safety References Summary Also included are lists of known teratogens, pregnancy drug registries, AHA endocarditis guidelines, FDA category definitions, and the percent of drugs assigned to them. Thanks go to Dr. Weiner for his ingenuity in taking a complicated problem and making it straightforward and simple for those who care for pregnant and nonpregnant women. This effort is the first to simultaneously embrace text and an electronic version for hand-held computers. The combination of Elsevier—the world's largest health sciences publisher—and Dr. Weiner—an individual who has a long- term interest in female reproduction and especially high-risk obstetrics—assures success of the project. This is the new frontier in medical publishing, and we will look forward to additions and revisions in the electronic format. Frederick P. Zuspan, MD Professor and Chairman, Emeritus The Ohio State University School of Medicine and Public Health Department of Obstetrics and Gynecology; Emeritus Editor American Journal of Obstetrics and Gynecology Las Vegas, Nevada This page intentionally left blank Foreword to the First Edition The study of medication use in pregnancy is one of the least developed and most neglected areas of clinical pharmacology and drug research. Although pregnancy is widely regarded as a special population due to both the unique maternal physiology and the vulnerability of the developing fetus, researchers and pharmaceutical companies have been reticent to evaluate optimal modalities of treatment for this group. The issue is compounded by the enormous number of medications women are exposed to during pregnancy. Epidemiological surveys indicate nearly two thirds of all pregnant women use four to five drugs during pregnancy through delivery. Women with medical conditions such as epilepsy, diabetes, and hypertension must continue therapy while pregnant. In some cases, due to a justified or unjustified concern for the developing fetus, the medication prescribed is either withheld, inadequate to treat the maternal condition, or not monitored closely enough as pregnancy progresses for needed adjustments in dosing. The result is a double negative, that of fetal exposure without maternal or fetal benefit. The lack of Food and Drug Administration obstetric labeling and the near universal off-label use of drugs are the direct result of the paucity of research and clinical trials in this special population. The public concern stems from the use of drugs in pregnancy based on an empiric approach rather than a scientific basis, and does not take into account the many alterations in pregnancy. There are profound physiologic changes in pregnancy involving the mother, placenta and fetus that may alter absorption, distribution and elimination of drugs. For example, there is a decrease in gastric emptying and an increase in intestinal transit time, both of which may alter gastrointestinal absorption of drugs. Similarly, the physiologic increase in pulmonary blood flow, hyperventilation, or increased tidal volume during pregnancy may increase the absorption of inhalants. The dramatic increase in blood volume with subsequent dilutional hypoalbuminemia, especially in the third trimester, can be associated with a decreased drug binding capacity and may profoundly affect the distribution of many drugs during pregnancy. These are but a few of the many examples of the complex changes in pregnancy that affect the type, dosing, and effectiveness of medications in this special population. Daily advances in therapeutics dramatically increase the number and types of medications available more rapidly than textbooks can be updated. This new text by Weiner and Buhimschi, Drugs for Pregnant and Lactating Women, helps fill the void. It is a comprehensive resource addressing the unique needs of this special population. Each drug entry includes the generic and trade names, drug class, indication(s) (on and off label), mechanism(s) of action, dosage, maternal and fetal considerations, breastfeeding safety, references, FDA pregnancy and lactation categories, and a summary. Wherever possible, evidence- based recommendations are made. This unique reference combines the printed word with an electronic version updated quarterly to allow for the incorporation of the new therapeutics. This design is user friendly for the busy clinician and includes prescribing information as well as a review of the published experience with the drug in pregnancy and lactation. As the first of its type, Drugs for Pregnant and Lactating Women will simplify the clinician’s ability to maintain updated information on medications in pregnancy and facilitate the incorporation of more rigorous study into the use of medications in the pregnant and lactating populations. Catherine Y. Spong, MD Chief, Pregnancy and Perinatology Branch PPB CRMC NICHD NIH Bethesda, Maryland This page intentionally left blank